For polymers introduced into a living body it is desirable that they be non-toxic and that their biodistribution be predictable. It is also desirable that such polymers should have a controlled distribution of molecular weights and a controlled composition of repeating units, as well as being biocompatible. Phosphorylcholine groups are a major component of the outer membranes of eukaryotic cells, and polymers containing phosphorylcholine groups can enhance the biocompatibility of materials comprising the polymer.
U.S. Pat. No. 6,214,957 to Shiino et al., issued Apr. 10, 2001, and U.S. Pat. No. 6,204,324 to Shuto et al., issued Mar. 20, 2001, teach that solubilizers, emulsifiers, and dispersing agents moisturize the skin when used as washing agents and elevate the concentration of a material to be solubilized, emulsified, or dispersed in solvents including water. The water-soluble random copolymers containing phosphorylcholine groups taught by U.S. Pat. Nos. 6,214,957 and 6,204,324 are prepared by conventional free radical methods. The conventional free radical methods used in these issued patents do not permit control of the distribution of molecular weights and the composition of repeating units in copolymers produced. Polymers, like those taught by U.S. Pat. Nos. 6,214,957 and 6,204,324, prepared using conventional free radical synthesis methods, are not optimal for introduction into a mammalian (e.g., human) body.
In medicine, a stent is any device which is inserted into a blood vessel or other internal duct in order to expand the vessel to prevent or alleviate a blockage. Such devices have been fabricated from metal mesh and remain in the body permanently or until removed through further surgical intervention. A bioresorbable stent can serve the same purpose, but is manufactured from a resorbable or absorbable material.
Percutaneous transluminal coronary angioplasty (PTCA) is a common procedure for treating heart disease. A problem associated with PTCA is the formation of intimal flaps or torn arterial linings which can collapse and occlude the conduit after the balloon used in PTCA is deflated. Moreover, thrombosis and restenosis of the artery can develop over several months after the procedure, which can require another angioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining, and to reduce the chance of the development of thrombosis and restenosis, a stent can be introduced in the lumen to maintain the vascular patency.
Stents can be used not only as a mechanical intervention but also as a vehicle for providing biological therapy (e.g., delivery of at least one bioactive agent). As a mechanical intervention, stents act as scaffolds, functioning to physically hold open and, if desired, to expand the wall of a passageway (e.g., a blood vessel). Biological therapy can be achieved by medicating a stent. Medicated stents provide for the local administration of a therapeutic substance at a desired site. Local delivery can produce fewer side effects and can achieve more favorable results.
The use of metal drug-eluting stents can present some potential drawbacks. These include a predisposition to late stent thrombosis (the forming of blood clots long after the stent is in place), prevention of late vessel adaptive or expansive remodeling, hindrance of surgical revascularization, and impairment of imaging with multislice computed tomography (CT).
To overcome some of these potential drawbacks, bioresorbable or bioabsorbable stents are being developed. Like metal stents, placement of a bioresorbable stent will restore blood flow and support the vessel through the healing process. However, in the case of a bioresorbable stent, the stent will gradually resorb and be benignly cleared from the body, leaving no permanent implant.
Studies have shown that the most critical period of vessel healing is largely complete by approximately three months. Therefore, the goal of a bioresorbable or “temporary” stent is to fully support the vessel during this critical period, and then resorb from the body when it is no longer needed.
A coronary stent is a tube placed in the coronary arteries that supply the heart, to keep the arteries open in the treatment of coronary heart disease. Coronary stents reduce chest pain and have been shown to improve survivability in the event of an acute myocardial infarction.
Similar stents and procedures are used in non-coronary vessels, e.g., in the legs in treating peripheral artery disease. One of the drawbacks of vascular stents is the potential for restenosis via the development of a thick smooth muscle tissue inside the lumen, the so-called neointima. Development of a neointima is variable but can at times be so severe as to re-occlude the vessel lumen (restenosis), especially in the case of smaller diameter vessels, which often results in reintervention. Consequently, current research focuses on the reduction of neointima after stent placement.
A drug-eluting stent (DES) is a peripheral or coronary stent (a scaffold) placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots (thrombus), could otherwise block the stented artery.
A coating, typically of a polymer, holds and elutes (releases) the drug into the arterial wall by contact transfer in a drug-eluting stent. The first drug-eluting stents used durable coatings, but some newer coatings are designed to biodegrade after or as the drug is eluted. Coatings are typically spray coated or dip coated. There can be one to three or more layers in the coating, e.g., a base layer for adhesion, a main layer for holding the drug, and sometimes a top coat to slow down the release of the drug and extend its effect.
Stents can be fabricated from materials that are biocompatible and/or biodegradable. The goal is for the stent to have a biocompatible coating which demonstrates great safety with regard to stent thrombosis. The stent coatings can, in some instances, lower acute and sub-acute thrombosis rates. The coating material selected must not only have sufficient mechanical properties but also show excellent coating integrity. The preceding problem has been at least partially ameliorated by the use of increasingly biocompatible materials and/or biocompatible coatings.
It would be beneficial to have biocompatible polymers that form biomembrane-like structures to enhance biocompatibility and/or bioabsorbability. Providing polymeric medical devices which are resorbable/bioabsorbable upon introduction into a mammal and that comprise polymers that can be excreted (intact or as a degradation product) in the host's urine would be beneficial. Medical devices that include a polymer coating which reduces complications (e.g., stent thrombosis) would be desirable. Such polymers and medical devices would be particularly useful for coronary stents, although they would also provide substantial benefit to any manner of other medical devices introduced into a mammal. Such medical devices (i.e., drug-eluting stents, among others) should also demonstrate excellent mechanical properties.